Bimatoprost/timolol fixed combination(BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

AIM：To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%（BTFC）in patients in Greece with primary open angle glaucoma（POAG）or ocular hypertension（OHT）whose previous therapy provided insufficient lowering of intraocular pressure（IOP）.·METHODS：A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS：A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg（=764;〈0.001）.In patients（=680）who replaced their previous IOP-lowering monotherapy（a single drug,or a fixed combination of 2drugs in a single ophthalmic drop）with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg（〈0.001）.IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as＂good＂or＂very good.＂Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION：In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension

Background Lowering intraocular pressure （lOP） is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China.In this study,we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.Methods In this multicenter,randomized,double-masked,parallel controlled study,patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1：1 ratio at 11 Chinese ophthalmic departments.Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03％ bimatoprost and 0.5％ timolol （followed by vehicle for masking） once daily at 19：00 P.M.and concurrent treatment was 0.03％ bimatoprost followed by 0.5％ timolol once daily at 19：00 P.M.The primary efficacy variable was change from baseline in mean diurnal intraocular pressure （IOP） at week 4 visit in the intent-to-treat （ITr） population.Primary analysis evaluated the non-inferiority of bimatoprost/timolol fixed combination to concurrent with respect to the primary variable using a confidence interval （CI） approach.Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95％ CI for the between-treatment （bimatoprost/timolol fixed combination minus concurrent） difference was-≤1.5 mmHg.Adverse events were collected and slit-lamp examinations were performed to assess safety.Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher＇s exact test.Results Of the enrolled 235 patients,121 patients were randomized to receive bimatoprost/timolol fixed combination and,114 patients were randomized to receive concurrent treatment.At baseline the mean value of mean diurnal IOP was （25.20±3.06） mmHg in the bimatoprost/timolol fixed combination group and （24.87±3.88） mmHg in the concurrent group.The difference between the treatment groups was not statistically significant.The mean change from baseline in mean diurnal IOP （±standard deviation） in the bimatoprost/timolol fixed combination group was （-9.38±4.66） mmHg and it was （-8.93±4.25） mmHg in the concurrent group （P ＜0.01）.The difference between the two treatment groups （bimatoprost/timolol fixed combination minus concurrent） in the change from baseline of mean diurnal IOP was-0.556 mmHg （95％ CI：-1.68,0.57,P=0.330）.The upper limit of the 95％ CI was less than 1.5 mmHg,the predefined margin of non-inferiority.Adverse events occurred in 26.4％ （32/121）of the bimatoprost/timolol fixed combination patients and 30.7％ （35/114） of the concurrent patients.The most frequent adverse event was conjunctival hyperemia,which was reported as treatment related in 16.5％ （20/121） in the bimatoprost/timolol fixed combination group and 18.4％（21/114） in the concurrent group （P ＞0.05）.Conclusions Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components.Safety profiles were similar between the treatment groups.

Comparative Evaluation of the Efficacy of the Bimatoprost 0.03%, Brimonidine 0.2%, Brinzolamide 1%, Dorzolamide 2%, and Travoprost 0.004%/Timolol 0.5%-Fixed Combinations in Patients Affected by Open-Angle Glaucoma

Purpose: This is a retrospective, comparative, head-to-head, not commissioned study about the efficacy of bimato-prost 0.03%, brimonidine 0.2%, brinzolamide 1%, dorzolamide 2%, and travoprost 0.004%/timolol 0.5%-fixed combinations in patients affected by na?ve open-angle glaucoma and IOP > 25 mmHg. Patients and Methods: Files from 70 patients (35 M, 35 F, mean age 69.52 y, S.D. 11.56, range: 37-87y) in our Glaucoma Service were retrospectively analyzed as long as 12 months. Every subgroup, including 14 age- and sex-matched patients, was allocated to 1 of the 5 groups of the fixed combinations monotherapy. Data recorded after 3 months follow-up were statistically analyzed by descriptive and ANOVA statistics as percentage of IOP reduction from baseline. Results: All the fixed combinations were effective in lowering IOP. The mean percentage reduction was: brimonidine/timolol 43.57%, dorzolamide/timolol 37.67%, bimatoprost/timolol 35.60%, travoprost/timolol 33.25% and brinzolamide/timolol 23.0%. The brimonidine/timolol fixed combination showed to be statistically significant more effective only than brinzolamide/timolol fixed combination (p = 0.001). Setting the α error to 5%, the power of the study is 26%, phi: 0.842. Discussion: In all this cohort of patients the target IOP was successfully achieved. All the fixed combinations used in this study had a very good profile of efficacy. Brimonidine, dorzolamide, bimatoprost and travoprost/timolol fixed combinations statistically significantly reduced the percentage of IOP from baseline (p = 0.001) more than brinzolamide/timolol fixed combination.

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.

Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy

AIM： To draw a Meta-analysis over the comparison of the intraocular pressure （lOP）-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs （PGAs） monotherapy. METHODS： After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials （RCTs） comparing the fixed combination of PGAs/timolol therapy （FCs） and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal lOP, percentage of participants whose lOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS： After six-month medical intervention, the mean diurnal lOP of FCs was lower than PGAs （MD -1.14, 95% CI -1.82 to -0.46, P=0.001）; the percentage of target lOP achieving between FCs and PGAs showed no significant difference （RR 1.18, 95% Cl 0.97 to 1.43, P=0.10）. No statistically significant differences of the incidence of hyperemia （RR 0.67, 95% CI 0.45 to 1.01, p=0.06） and eye irritation （RR 1.20, 95% CI 0.95 to 1.51, P=0.12） between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects （central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% Cl -0.02 to 0.00, P=0.23）. The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION： The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering lOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.

Efficacy and safety of latanoprost/timolol fixed combination dosed twice daily compared to once daily in patients with primary open angle glaucoma

AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.

A 4-year retrospective study of add-on therapy to the fixed combination of dorzolamide/timolol for the treatment of POAG

AIM:To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma(POAG)and the addition of other intraocular pressure(IOP)lowering medications such as prostaglandin analogs and brimonidine.METHODS:A retrospective,non-randomized,and descriptive clinical study was performed with 182 eyes diagnosed with POAG.Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only,a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol,and a third group with the addition of brimonidine to the same fixed combination.IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS:IOP was reduced satisfactorily in all three groups;however,a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs.In this group,a progressive,significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION:IOP reduction was efficacious in all three groups.The addition of prostaglandin analogs showed progressive IOP reduction,progressive responseand absence of long-term drift.Brimonidine did not show a significant additive effect.

Switching Study of Tafluprost/Timolol Fixed-Combination Ophthalmic Solution, Following Unfixed Combination of Tafluprost Ophthalmic Solution 0.0015% and Timolol Ophthalmic Gel-Forming Solution 0.5%

Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.

Efficacy and Safety of Travoprost and Timolol Fixed Combination Compared to Travoprost in Patients with Primary Open Angle Glaucoma and Ocular Hypertension

Purpose: To compare intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and travoprost 0.004% and beta-blocker 0.5% fixed combination ophthalmic solution in patients with open-angle glaucoma and ocular hypertension. Methods: In this prospective, multicentre clinical trial, 62 patients received travoprost 0.004% (n = 31) or travoprost 0.004% and beta-blocker 0.5% fixed combination (n = 31). Efficacy and safety were compared across treatment groups over 2 years. IOP reduction and adverse events were examined at 3, 6, 12 and 24 months for each group. Results: Mean IOP at the first visit in the travoprost 0.004% group was 26.4 (SD ± 2.1), and travoprost 0.004%/timolol 0.5% group was 26.3 (SD ± 2.1). Mean IOP after 24 months in the travoprost 0.004% group was 20.5 (SD ± 1.5) and travoprost 0.004%/timolol 0.5% group was 18.5 (SD ± 1.5). There were statistically significant differences in IOP in both eyes after third visit (after 1 year) and fourth visit (after 2 years). Conclusion: After 2 year of treatment, travoprost 0.004%/timolol 0.5% produced clinically relevant IOP reductions in patients with open-angle glaucoma or ocular hypertension that were greater than those produced by travoprost 0.004% alone.

Ocular Surface Disease Index in Glaucomatous Patients Treated with Bimatoprost

Objectives: To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of bimatoprost 0.03%/timolol 0.50%, timolol 0.50% or bimatoprost 0.01% eye drops. Methods: This is a prospective, one center, open-label clinical trial. It was performed on 60 glaucoma patients between 01-01-2012 and 12-31-2012. These patients were randomly divided in three subgroups: bimatoprost 0.03%/timolol 0.50% fixed combination, timolol 0.50% and bimatoprost 0.01%. The Ocular Surface Disease Index (O.S.D.I.) was evaluated in all the glaucomatous patients of the three subgroups at basal time and after 6 and 12 months. All the results were statistically evaluated by Student t-test and one-way ANOVA. The results were considered statistically significant if p < 0.05. Results: All of the patients ended the clinical trial. There was no statistical significant difference between patients treated with the bimatoprost 0.03%/timolol 0.50% fixed combination and timolol 0.50% eye drops alone (p = 0.845). Instead, there was a statistically significant difference between bimatoprost 0.01% and bimatoprost 0.03%/timolol 0.50% patients (p = 0.05) and between bimatoprost 0.01% and timolol 0.50% eye drops alone (p = 0.049). Conclusions: This is a clinical trial based not on the hypotonising effect of these drugs but on their tolerability. The drug which showed the best tolerability is bimatoprost 0.01%.

噻吗洛尔与贝美前列素联合治疗开角型青光眼和高眼压症的临床效果研究

目的:探讨噻吗洛尔与贝美前列素联合治疗开角型青光眼和高眼压症的临床效果。方法:选择原发性开角型青光眼患者13例,分为噻吗洛尔组和联合用药组,联合组滴用0.03%贝美前列腺素每日1次和0.5%噻吗洛尔每日2次,疗程均为12周。噻吗洛尔组仅仅使用0.5%噻吗洛尔每日2次;治疗前、治疗后1月、2月及3月随访,测量眼压并观察眼局部及全身不良反应;对所有患者详细记录治疗前及治疗后用Goldmann压平眼压计测量的眼压,眼压测定时间为上午8时、11时,下午4时。结果:用药1个月、2个月、3个月与用药前比较,差异均有统计学意义,P<0.05;A组和B组,两组比较差异无统计学意义,P>0.05,但A组,平均降压幅度大于B组,且长时间维持眼压水平更为稳定;在一天的各时段,0.03%的联合用药每日1次的降眼压效果较0.5%的噻吗洛尔每日2次的降眼压效果明显(P<0.01),两组比较差异有统计学意义,P<0.05,且每日内贝美前列腺素联合组,维持眼压水平更为稳定。结论:噻吗洛尔与贝美前列素联合组降眼压疗效明确,且无明显毒副作用。

剥脱性青光眼患者的临床诊治体会

目的对来本院就诊的剥脱性青光眼患者行手术及术后药物治疗,总结其诊断要点及治疗经验,以供临床参考。方法本研究为1例82岁确诊为剥脱性青光眼的男性患者实施白内障超声乳化术,依据其眼部典型的临床体征,结合超声生物显微镜、光学相干断层扫描等辅助检查做出剥脱性青光眼的诊断;并将术中所取晶状体前囊膜行电镜扫描观察其结构,探讨眼压升高的机制。追踪其术后3个月的视力、眼压及视野变化情况。结果患者术后1周,左眼视力0.4,眼压12 mmHg(1 mmHg=0.133 kPa)。术后1个月,左眼视力0.5,眼压15 mmHg,人工晶状体正位。术后2个月,左眼视力0.6,眼压22 mmHg,人工晶状体轻度后倾位,无中心偏移。术后3个月,左眼视力0.8,眼压27 mmHg,人工晶状体位置较前无明显变化,使用拉坦复合制剂滴眼1周后,测得左眼视力0.8,眼压14 mmHg,此后平均眼压基本稳定在14 mmHg,控制效果理想。结论剥脱性青光眼患者行白内障超声乳化手术,术后局部辅以拉坦复合制剂治疗,对眼压控制和视功能恢复有较好疗效。